Excitatory synaptic input leads to neuronal firing if its intensity is sufficient to reach a threshold depolarization. The requisite intensity for firing, however, is adjusted by synaptic inhibition. In the olfactory system, the mitral and tufted cells of the olfactory bulb serve as the excitatory link between the olfactory receptors and the cortex. The first stage of inhibition of mitral/tufted cells is provided by periglomerular cells through both feedforward and feedback pathways. The general aim of this proposal is to determine the role of periglomerular cells in mitral/tufted cell inhibition. Patch clamp techniques will be used to record from neurons in acute slices of rat olfactory bulb. A large subpopulation of periglomerular cells release the inhibitory transmitter GABA onto mitral/tufted cells and also onto themselves, resulting in self-inhibition. The proposed research will determine the strength of this self-inhibition, whether neighboring, otherwise inactive, periglomerular cells are also inhibited by spillover, and whether GABA release from periglomerular cells is altered by endogenous transmitters. Simultaneous recordings from pairs of periglomerular cells and pairs of periglomerular and mitral/tufted cells will determine whether action potentials are necessary to evoke release from these cell types, and measure the strength and effects of transmitter spillover from release sites to extrasynaptic and neighboring synaptic receptors. The firing pattern of individual neurons is the basic unit of neuronal circuit behavior. Firing patterns are, in turn, dependent on the rules by which single neurons integrate synaptic inputs. An understanding of synaptic integration requires knowledge of the temporal and spatial properties of synaptic inhibition and excitation. Studies such as those proposed herein will determine how mechanisms of synaptic transmission through direct connections, as well as through spillover, affect integration and firing properties and will therefore provide a basis for understanding olfactory information processing.